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IMPORTANT CORRECTION OF DRUG INFORMATION about EMBEDA(R) (morphine sulfate and naltrexone hydrochloride) Extended Release Capsules for oral use C-II

March 26, 2010

BRISTOL, Tenn., March 26 /PRNewswire-FirstCall/ –


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    |                                 IMPORTANT                             |
    |                                CORRECTION                             |
    |                                  OF DRUG                              |
    |                                INFORMATION                            |
    |                                                                       |
    |                                   about                               |
    |               EMBEDA(R) (morphine sulfate and naltrexone              |
    |           hydrochloride) Extended Release Capsules for oral use       |
    |                                    C-II                               |
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On October 8, 2009, King Pharmaceuticals, Inc. (King) received a Warning Letter from the Division of Drug Marketing, Advertising, and Communications (DDMAC) at the Food and Drug Administration (FDA) regarding two video news releases – EMBEDA Media backgrounder, and EMBEDA Visual Media Technology (news releases), for EMBEDA® (morphine sulfate and naltrexone hydrochloride) Extended Release Capsules for oral use C-II (EMBEDA). The FDA stated that the news releases were false or misleading because they omitted and minimized the risks associated with EMBEDA, failed to present the limitations to its approved indication, and presented misleading claims about EMBEDA.

To correct any false or misleading impression you may have gained from the news releases, King is providing you with the following clarifying information about EMBEDA.


    1.      The news releases presented numerous efficacy claims regarding
            EMBEDA but entirely failed to disclose the potential for fatal
            risks associated with EMBEDA.

    Important information regarding potentially fatal risks associated with
    EMBEDA follows:

        - The co-ingestion of alcohol with EMBEDA may result in an increase of
          plasma levels and potentially fatal overdose of morphine.
        - EMBEDA is to be swallowed whole or the contents of the capsules
          sprinkled on apple sauce. The pellets in the capsules are not to be
          crushed, dissolved, or chewed due to the risk of rapid release and
          absorption of a potentially fatal dose of morphine.
        - EMBEDA 100 mg/4 mg IS FOR USE IN OPIOID-TOLERANT PATIENTS ONLY.
          Ingestion of these capsules or pellets within the capsules may cause
          fatal respiratory depression when administered to patients not
          already tolerant to high doses of opioids.
        - Crushing, chewing, or dissolving EMBEDA will also result in the
          release of naltrexone which may precipitate withdrawal in opioid-
          tolerant individuals.

    These are not all of the risks associated with EMBEDA. For a complete
    description, please see the additional risk disclosures below and the full
    Prescribing Information (PI).

    2.    The news releases failed to disclose important limitations to
          EMBEDA's indication. Therefore, the news releases implied that
          EMBEDA is useful in a broader range of conditions or patients than
          has been demonstrated by substantial evidence or substantial
          clinical experience.

    The news releases failed to disclose that EMBEDA is not intended for
    acute/postoperative pain or if the pain is mild or not expected to persist
    for an extended period of time. EMBEDA is only indicated for postoperative
    pain when the patient is already receiving chronic opioid therapy or if
    the pain is expected to be moderate to severe and persist for an extended
    period of time. The FDA approved product labeling (PI) for EMBEDA
    specifically states:

          EMBEDA is an extended-release oral formulation of morphine sulfate
          and naltrexone hydrochloride indicated for the management of
          moderate to severe pain when a continuous, around-the-clock opioid
          analgesic is needed for an extended period of time.
          EMBEDA is NOT intended for use as a prn analgesic.
          EMBEDA is not indicated for acute/postoperative pain or if the pain
          is mild or not expected to persist for an extended period of time.
          EMBEDA is only indicated for postoperative use if the patient is
          already receiving chronic opioid therapy prior to surgery or if the
          postoperative pain is expected to be moderate to severe and persist
          for an extended period of time. Physicians should individualize
          treatment, moving from parenteral to oral analgesics as appropriate.

    3.    The news releases presented misleading claims that imply that
          EMBEDA's pharmacological properties have been shown to have a
          clinically significant effect in reducing liking and euphoria and
          that the naltrexone in EMBEDA will reverse the subjective and
          analgesic effects of morphine, thus reducing the likelihood of
          morphine overdose if the drug is crushed, chewed, or dissolved.

    EMBEDA's formulation has not been shown to confer abuse resistance and
    reduced abuse liability. According to the FDA approved PI:

          The pharmacodynamic effect of naltrexone in the setting of crushed
          EMBEDA was examined in two clinical trials. In a randomized double-
          blind, triple-dummy, four-way cross-over study, 32 non-dependent
          recreational opioid users received 120 mg of EMBEDA whole and
          crushed, 120 mg of immediate-release morphine sulfate and placebo.
          Overall, 87.5% of subjects had some degree of reduced drug liking
          after receiving crushed EMBEDA, while 12.5% had no reduction in drug
          liking. There was considerable individual variability in the degree
          of reduction in drug liking, ranging between 10 and 50%. Similarly,
          69% of subjects showed some degree of a decrease in euphoria with
          crushed EMBEDA compared to IR morphine and 31% of subjects did not
          report a reduction in euphoria. There was similar individual
          variability in the degree of reduction in euphoria.

          A randomized double-blind, placebo-controlled, three-way cross-over
          trial in 28 non-dependent recreational opioid users was performed
          using 30 mg of IV morphine alone and 30 mg of IV morphine in
          combination with 1.2 mg of IV naltrexone to simulate parenteral use
          of crushed EMBEDA. The combination of morphine with naltrexone
          resulted in 71% of subjects reporting a reduction in euphoria
          compared to morphine alone. Note that the intravenous injection of
          crushed EMBEDA may result in serious injury and death due to a
          morphine overdose or an embolic event. Intravenous injection of
          crushed EMBEDA may precipitate a severe withdrawal syndrome in
          opioid-dependent patients.

          The clinical significance of the degree of reduction in drug liking
          and euphoria reported in these studies has not yet been established.
          There is no evidence that the naltrexone in EMBEDA reduces the abuse
          liability of EMBEDA.

    4.    Other important risks omitted from the news releases included the
          following:

    The PI for EMBEDA includes the following boxed warning:


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    | WARNING: EMBEDA(R) capsules contain morphine, an opioid agonist and |
    | a Schedule II controlled substance with an abuse liability similar  |
    | to other opioid agonists. EMBEDA can be abused in a manner similar  |
    | to other opioid agonists, legal or illicit. This should be          |
    | considered when prescribing or dispensing EMBEDA in situations      |
    | where the physician or pharmacist is concerned about an increased   |
    | risk of misuse, abuse, or diversion.                                |
    |                                                                     |
    | EMBEDA contains pellets of an extended-release oral formulation of  |
    | morphine sulfate, an opioid receptor agonist, surrounding an inner  |
    | core of naltrexone hydrochloride, an opioid receptor antagonist     |
    | indicated for the management of moderate to severe pain when a      |
    | continuous, around-the-clock opioid analgesic is needed for an      |
    | extended period of time.                                            |
    |                                                                     |
    | EMBEDA is NOT intended for use as a prn analgesic.                  |
    |                                                                     |
    | EMBEDA 100 mg/4 mg IS FOR USE IN OPIOID-TOLERANT PATIENTS ONLY.     |
    | Ingestion of these capsules or the pellets within the capsules may  |
    | cause fatal respiratory depression when administered to patients    |
    | not already tolerant to high doses of opioids.                      |
    |                                                                     |
    | Patients should not consume alcoholic beverages while on EMBEDA     |
    | therapy. Additionally, patients must not use prescription or non-   |
    | prescription medications containing alcohol while on EMBEDA         |
    | therapy. The co-ingestion of alcohol with EMBEDA may result in an   |
    | increase of plasma levels and potentially fatal overdose of         |
    | morphine. EMBEDA is to be swallowed whole or the contents of the    |
    | capsules sprinkled on apple sauce. The pellets in the capsules are  |
    | not to be crushed, dissolved, or chewed due to the risk of rapid    |
    | release and absorption of a potentially fatal dose of morphine.     |
    |                                                                     |
    | Crushing, chewing, or dissolving EMBEDA will also result in the     |
    | release of naltrexone which may precipitate withdrawal in opioid-   |
    | tolerant individuals.                                               |
    -----------------------------------------------------------------------

In addition, EMBEDA is associated with a number of serious adverse reactions:

Serious adverse reactions that may be associated with EMBEDA therapy in clinical use include: respiratory depression, respiratory arrest, apnea, circulatory depression, cardiac arrest, hypotension, and/or shock.

For further information please refer to full prescribing information at the following link: www.EMBEDA.com.

[Full approved indication]

EMBEDA is an extended-release oral formulation of morphine sulfate and naltrexone hydrochloride indicated for the management of moderate to severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time.

EMBEDA is NOT intended for use as a prn analgesic.

EMBEDA is not indicated for acute/postoperative pain or if the pain is mild or not expected to persist for an extended period of time. EMBEDA is only indicated for postoperative use if the patient is already receiving chronic opioid therapy prior to surgery or if the postoperative pain is expected to be moderate to severe and persist for an extended period of time. Physicians should individualize treatment, moving from parenteral to oral analgesics as appropriate.


    Eric G. Carter, Ph.D., M.D.
    Chief Science Officer

    CONTACT:
    Jack Howarth
    Vice President
    Investor Relations
    +1-908-429-8350

EMBEDA is a registered trademark of Alpharma Pharmaceuticals LLC, a subsidiary of King Pharmaceuticals®, Inc.

Copyright © 2010 King Pharmaceuticals®, Inc. All rights reserved. EMB7108 03/2010

SOURCE King Pharmaceuticals, Inc.


Source: newswire



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